title: Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53.
abstract: IFI16 is a member of the interferon-inducible HIN-200 family of nuclear proteins. It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor protein and other transcription factors. However, the mechanisms of interaction remain unknown. Here, we report the crystal structures of both HIN-A and HIN-B domains of IFI16 determined at 2.0 and 2.35 Å resolution, respectively. Each HIN domain comprises a pair of tightly packed OB-fold subdomains that appear to act as a single unit. We show that both HIN domains of IFI16 are capable of enhancing p53-DNA complex formation and transcriptional activation via distinctive means. HIN-A domain binds to the basic C terminus of p53, whereas the HIN-B domain binds to the core DNA-binding region of p53. Both interactions are compatible with the DNA-bound state of p53 and together contribute to the effect of full-length IFI16 on p53-DNA complex formation and transcriptional activation.
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C4, Canada.
authors.forename: Jack C C
authors.initials: JC
authors.lastname: Liao
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.forename: Vaclav
authors.initials: V
authors.lastname: Brazda
authors.forename: Shili
authors.initials: S
authors.lastname: Duan
authors.forename: Mani
authors.initials: M
authors.lastname: Ravichandran
authors.forename: Justin
authors.initials: J
authors.lastname: Ma
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.forename: Yun-Xing
authors.initials: YX
authors.lastname: Wang
authors.forename: Nickolay Y
authors.initials: NY
authors.lastname: Chirgadze
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; C076700:IFI16 protein, human; D004247:DNA; D007372:Interferons